Functional characterization of human organic cation transporter OCTN1 single nucleotide polymorphisms in the Japanese population

摘要: The organic cation transporter OCTN1 (SLC22A4) is expressed ubiquitously, with strong expression in kidney, trachea, bone marrow, and fetal liver, it mediates transport of cations a pH‐dependent manner. Recent studies have identified single nucleotide polymorphisms (SNPs) the Japanese population. Two SNPs present exon regions, c1063t g1531a, cause amino acid mutation, Thr306Ile (T306I) Gly462Glu (G462E), respectively. We examined influence these on intracellular localization, protein expression, activity OCTN1. Immunocytochemical analysis showed similar localizations cellular membranes HEK293 cells transiently transfected an plasmid DNA for or its SNP allelic variants. Km Vmax values tetraethylammonium (TEA) uptake by T306I were to those wild‐type even when value was normalized level protein. In contrast, G462E had almost negligible activity, although equivalent that wild‐type. conclude causes mutation does not affect TEA whereas abrogates presumably affecting physiological function and/or pharmacological characteristics substrates. © 2004 Wiley‐Liss, Inc. American Pharmacists Association J Pharm Sci 93:2920–2926,